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BACKGROUND: Biomarkers of inflammation predictive of cystic fibrosis (CF) disease outcomes would increase the power of clinical trials and contribute to better personalization of clinical assessments. A representative patient cohort would improve searching for believable, generalizable, reproducible and accurate biomarkers. METHODS: We recruited patients from Mountain West CF Consortium (MWCFC) care centers for prospective observational study of sputum biomarkers of inflammation. After informed consent, centers enrolled randomly selected patients with CF who were clinically stable sputum producers, 12 years of age and older, without previous organ transplantation. RESULTS: From December 8, 2014 through January 16, 2016, we enrolled 114 patients (53 male) with CF with continuing data collection. Baseline characteristics included mean age 27 years (SD = 12), 80% predicted forced expiratory volume in 1 s (SD = 23%), 1.0 prior year pulmonary exacerbations (SD = 1.2), home elevation 328 m (SD = 112) above sea level. Compared with other patients in the US CF Foundation Patient Registry (CFFPR) in 2014, MWCFC patients had similar distribution of sex, age, lung function, weight and rates of exacerbations, diabetes, pancreatic insufficiency, CF-related arthropathy and airway infections including methicillin-sensitive or -resistant Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia complex, fungal and non-tuberculous Mycobacteria infections. They received CF-specific treatments at similar frequencies. CONCLUSIONS: Randomly-selected, sputum-producing patients within the MWCFC represent sputum-producing patients in the CFFPR. They have similar characteristics, lung function and frequencies of pulmonary exacerbations, microbial infections and use of CF-specific treatments. These findings will plausibly make future interpretations of quantitative measurements of inflammatory biomarkers generalizable to sputum-producing patients in the CFFPR.
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Fibrosis Quística/patología , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Selección de Paciente , Esputo/microbiología , Infecciones Estafilocócicas/patología , Adolescente , Adulto , Fibrosis Quística/microbiología , Fibrosis Quística/terapia , Femenino , Humanos , Pulmón/microbiología , Pulmón/patología , Pulmón/fisiopatología , Masculino , Staphylococcus aureus Resistente a Meticilina/fisiología , Persona de Mediana Edad , Estudios Prospectivos , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/terapia , Adulto JovenRESUMEN
Airway inflammation underlies cystic fibrosis (CF) pulmonary exacerbations. In a prospective multicenter study of randomly selected, clinically stable adolescents and adults, we assessed relationships between 24 inflammation-associated molecules and the future occurrence of CF pulmonary exacerbation using proportional hazards models. We explored relationships for potential confounding or mediation by clinical factors and assessed sensitivities to treatments including CF transmembrane regulator (CFTR) protein synthesis modulators. Results from 114 participants, including seven on ivacaftor or lumacaftor-ivacaftor, representative of the US CF population during the study period, identified 10 biomarkers associated with future exacerbations mediated by percent predicted forced expiratory volume in 1 s. The findings were not sensitive to anti-inflammatory, antibiotic, and CFTR modulator treatments. The analyses suggest that combination treatments addressing RAGE-axis inflammation, protease-mediated injury, and oxidative stress might prevent pulmonary exacerbations. Our work may apply to other airway inflammatory diseases such as bronchiectasis and the acute respiratory distress syndrome.
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STUDY OBJECTIVE: To evaluate outcomes of children after ovarian-sparing surgery (OSS) for non-neoplastic and benign neoplastic ovarian lesions. DESIGN: Retrospective cohort study from January 2003 to January 2012. SETTING: Single, high-volume, tertiary care hospital. PARTICIPANTS: Children 18 years of age and younger. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Postoperative complications and tumor recurrence after OSS. RESULTS: One hundred nine patients underwent OSS with a median age of 13.3 years (interquartile range [IQR], 11.4-15.1 years). Eighty-two patients were treated laparoscopically with 4 conversions to an open procedure. Postoperative complications included surgical site infections in 7 patients (6%). Pathology most commonly revealed functional ovarian cysts (n = 57) and mature teratomas (n = 37). Ninety-four patients (86%) were followed for a median of 10.4 months (IQR, 0.72-30.8 months). Fifty-five patients (60%) had subsequent imaging surveillance a median of 7.6 months postoperatively (IQR, 3.9-13 months). Ten patients (10%) developed a second ipsilateral lesion within a median time of 11 months (IQR, 7.7-24 months), of whom 5 girls had repeated surgery for mass enlargement or persistent abdominal pain at a median time of 10.5 months (IQR, 8.0-12.65 months). Fifty-eight patients (63%) began or resumed menses at their most recent follow-up. Three girls became pregnant after OSS at a median follow-up of 5 years (range, 2.4-6.7 years). CONCLUSION: Benign ovarian lesions in children can be treated successfully with OSS with low recurrence and repeat surgery rates.
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Tratamientos Conservadores del Órgano/métodos , Neoplasias Ováricas/cirugía , Ovario/cirugía , Adolescente , Niño , Estudios de Cohortes , Femenino , Humanos , Laparoscopía , Recurrencia Local de Neoplasia/cirugía , Tratamientos Conservadores del Órgano/efectos adversos , Ovario/patología , Pediatría , Complicaciones Posoperatorias/epidemiología , Embarazo , Reoperación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Preoperative evaluation of ovarian tumors for malignancy is essential to determine appropriate treatment. Our study assessed the utility of ovarian lesion volumes to screen for malignancy in adolescent ovarian lesions. METHODS: A retrospective chart review of adolescent patients (8-18years) who underwent an ovarian operation from January 2008 to December 2012. Data included demographics, ultrasonographic volume measurements, and tumor markers. Volumes were calculated using the prolate ellipsoid formula. Data are presented as medians. RESULTS: One hundred twenty-three females were included at a median age of 13.7years (IQR 12.5-16). Eight patients had malignancies. The median benign lesion volume was significantly smaller than malignant [152cm3 (IQR 57-592)vs. 1548cm(3) (IQR 627-2105), p=0.001]. A receiver operating characteristic (ROC) curve analysis (AUC 0.84, p=0.001) revealed a threshold ovarian lesion volume of <184cm(3) (100% sensitivity, 54% specificity, NPV 100%, PPV 13%) to accurately screen for malignancy. This held true when applied to our dataset as none of the 62 girls with volumes <184cm(3) had malignant pathology. CONCLUSIONS: This is the first documented use of ovarian lesion volumes as a screening tool in adolescent ovarian lesions. This should be used in conjunction with tumor markers and other imaging features to better screen for malignancy.